scholarly journals Molecular Epidemiology of Parasitic Diseases: The Chagas Disease Model

Author(s):  
Juan David ◽  
Felipe Guhl
Author(s):  
Janeesh A. Plakkal ◽  
Kezia Lizardo ◽  
Sean Wang ◽  
Edward Yurkow ◽  
Jyothi F. Nagajyothi

Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor (P-elF2α) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Dunia Margarita Medina-Buelvas ◽  
Elizabet Estrada-Muñiz ◽  
Miriam Rodríguez-Sosa ◽  
Mineko Shibayama ◽  
Libia Vega

AbstractSome reports suggest that exposure to organophosphorus (OP) pesticides increases the incidence of infections. Ethylated dialkylphosphates (EtDAPs) are metabolites of OP pesticides widely distributed with immunomodulatory potential. Chagas disease is produced by Trypanosoma cruzi parasites, and resolution of this infection requires the activation of inflammatory macrophages (MΦ), which results in cardiac fibrosis. Some reports indicate that EtDAPs increase the amount of the anti-inflammatory alternatively activated MΦ (M2; CD206+F4/80+). Therefore, we analyzed the course of T. cruzi infection, MΦ profiles from peritoneal exudate cells (PECs), inflammatory cell infiltration and fibrosis in the heart of BALB/c mice exposed to diethyldithiophosphate (DEDTP), diethylthiophosphate (DETP) or diethylphosphate (DEP, 0.01 g/kg), common DAPs produced by OP pesticides, 24 h before infection with T. cruzi. We found that DEDTP increased the parasite burden in blood by 99% at the peak of the infection and enhanced the myocardial damage due to an increase in infiltrated inflammatory cells (induced by DEDTP or DETP) and fibrosis (induced by EtDAPs). In the PECs, exposure to EtDAPs increased the proportion of the MΦ subpopulations of M2a, M2b and M2d, which are associated with tissue repair. These results indicate that exposure to EtDAPs can exacerbate the acute phase of a parasitic infection and increase the long-term damage to the heart.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Y. Flores-García ◽  
J. L. Rosales-Encina ◽  
V. H. Rosales-García ◽  
A. R. Satoskar ◽  
P. Talamás-Rohana

Currently, there is a considerable controversy over the participation of Treg cells duringTrypanosoma cruziinfection, the main point being whether these cells play a negative or a positive role. In this work, we found that the adoptive transfer of CD4+CD25+FOXP3+T cells from rSSP4- (a recombinantTrypanosoma cruziamastigote derived protein, previously shown to have immunomodulatory properties on macrophages) immunized BALB/c donors into syngenic recipients simultaneously withT. cruzichallenge reduces cardiac inflammation and prolongs hosts’ survival but increases blood parasitemia and parasite loads in the heart. These CD4+CD25+FOXP3+Treg cells from immunized mice have a relatively TGF-β-dependent suppressive activity on CD4+T cells. Therefore, regulatory CD4+CD25+T cells play a positive role in the development of acuteT. cruziinfection by inducing immunosuppressive activity that controls early cardiac inflammation during acute Chagas disease, prolonging survival, but at the same time promoting parasite growth.


Parasitology ◽  
2009 ◽  
Vol 136 (12) ◽  
pp. 1509-1528 ◽  
Author(s):  
M. A. MILES ◽  
M. S. LLEWELLYN ◽  
M. D. LEWIS ◽  
M. YEO ◽  
R. BALEELA ◽  
...  

SUMMARYTrypanosoma cruzi is the protozoan agent of Chagas disease, and the most important parasitic disease in Latin America. Protozoa of the genus Leishmania are global agents of visceral and cutaneous leishmaniasis, fatal and disfiguring diseases. In the 1970s multilocus enzyme electrophoresis demonstrated that T. cruzi is a heterogeneous complex. Six zymodemes were described, corresponding with currently recognized lineages, TcI and TcIIa-e – now defined by multiple genetic markers. Molecular epidemiology has substantially resolved the phylogeography and ecological niches of the T. cruzi lineages. Genetic hybridization has fundamentally influenced T. cruzi evolution and epidemiology of Chagas disease. Genetic exchange of T. cruzi in vitro involves fusion of diploids and genome erosion, producing aneuploid hybrids. Transgenic fluorescent clones are new tools to elucidate molecular genetics and phenotypic variation. We speculate that pericardial sequestration plays a role in pathogenesis. Multilocus sequence typing, microsatellites and, ultimately, comparative genomics are improving understanding of T. cruzi population genetics. Similarly, in Leishmania, genetic groups have been defined, including epidemiologically important hybrids; genetic exchange can occur in the sand fly vector. We describe the profound impact of this parallel research on genetic diversity of T. cruzi and Leishmania, in the context of epidemiology, taxonomy and disease control.


2019 ◽  
Author(s):  
Labanté Outcha Daré ◽  
Pierre-Emile Bruand ◽  
Daniel Gérard ◽  
Benoît Marin ◽  
Valérie Lameyre ◽  
...  

Abstract Although they are declining worldwide, neurotropic parasitic diseases are still common in developing and emerging countries. The aim of this study was to estimate the pooled prevalence and pooled association measures of comorbidities between mental disorders (anxiety, depression, bipolar disorder, and schizophrenia) and neurotropic parasitic diseases (malaria, cysticercosis, toxoplasmosis, human African trypanosomiasis, Chagas disease, and human toxocariasis) in developing and emerging countries. As the first meta-analysis on this topic, this study was performed in accordance with PRISMA guidelines. The protocol was registered in PROSPERO (N°CRD42017056521). The Medline, Embase, Lilacs, and Institute of Epidemiology and Tropical Neurology databases were used to search for articles without any restriction in language or date. We evaluated the quality of studies independently by two investigators using the Downs and Black assessment grid and pooled estimates using the random-effects method from CMA (Comprehensive Meta Analysis) Version 3.0. In total, 18 studies published between 1997 and 2016 met our inclusion criteria. We found that the prevalence of anxiety and depression in people suffering from Chagas disease and/or neurocysticercosis was 44.9% (95% CI, 34.4 – 55.9). In 16 pooled studies that included 1,782 people with mental disorders and 1,776 controls, toxoplasmosis and/or toxocariasis were associated with increased risk of schizophrenia and/or bipolar disorders (odds ratio = 2.3; 95% CI, 1.7 – 3.2). Finally, toxocariasis and/or toxoplasmosis were associated with an increased risk of the onset of schizophrenia (odds ratio = 2.4; 95% CI, 1.7 – 3.4). Our pooled estimates show that the associations between diseases studied are relatively high in developing and emerging countries. This meta-analysis supports the hypothesis that toxoplasmosis could be the cause of schizophrenia. These findings could prove useful to researchers who want to further explore and understand the associations studied. Keywords: Meta-analysis, association, co-morbidities, mental disorders, neurotropic parasitic diseases.


2019 ◽  
Author(s):  
Labanté Outcha Daré ◽  
Pierre-Emile Bruand ◽  
Daniel Gérard ◽  
Benoît Marin ◽  
Valérie Lameyre ◽  
...  

Abstract Background Although they are declining worldwide, neurotropic parasitic diseases are still common in developing and emerging countries. The aim of this study was to estimate the pooled prevalence and pooled association measures of comorbidities between mental disorders (anxiety, depression, bipolar disorder, and schizophrenia) and neurotropic parasitic diseases (malaria, cysticercosis, toxoplasmosis, human African trypanosomiasis, Chagas disease, and human toxocariasis) in developing and emerging countries.Methods As the first meta-analysis on this topic, this study was performed in accordance with PRISMA guidelines. The protocol was registered in PROSPERO (N°CRD42017056521). The Medline, Embase, Lilacs, and Institute of Epidemiology and Tropical Neurology databases were used to search for articles without any restriction in language or date. We evaluated the quality of studies independently by two investigators using the Downs and Black assessment grid and pooled estimates using the random-effects method from CMA (Comprehensive Meta Analysis) Version 3.0.Results In total, 18 studies studies published between 1997 and 2016 met our inclusion criteria. We found that the prevalence of anxiety and depression in people suffering from Chagas disease and/or neurocysticercosis was 44.9% (95% CI, 34.4 – 55.9). In 16 pooled studies that included 1,782 people with mental disorders and 1,776 controls, mental disorders (schizophrenia and/or bipolar disorders) were associated with increased risk of toxoplasmosis and/or toxocariasis (odds ratio = 2.3; 95% CI, 1.7 – 3.2). Finally, schizophrenia was associated with an increased risk of the onset of toxocariasis and/or toxoplasmosis (odds ratio = 2.4 / 95% CI, 1.7 – 3.4).Conclusion Our pooled estimates show that the association between neurotropic parasitic diseases among people with related mental disorders, and mental disorders among people with neurotropic parasitic diseases are relatively high in developing and emerging countries even though most studies have been found in Asia. This meta-analysis could prove useful to researchers who want to further explore and understand the associations between mental disorders and neurotropic patristic diseases in developing and emerging countries.


2013 ◽  
Vol 7 (2) ◽  
pp. e2041 ◽  
Author(s):  
Juan David Ramírez ◽  
Marleny Montilla ◽  
Zulma M. Cucunubá ◽  
Astrid Carolina Floréz ◽  
Pilar Zambrano ◽  
...  

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S429-S430
Author(s):  
Rebecca J Chancey ◽  
Yon Yu ◽  
Patricia Yu ◽  
Julian Jolly ◽  
Susan Montgomery

Abstract Background The Centers for Disease Control and Prevention’s (CDC) support to clinicians includes providing access to certain drugs exclusively available through CDC for diseases that lack, or have limited market availability of, FDA-approved therapeutics in the U.S. These drugs are provided by CDC under expanded access Investigational New Drug (IND) applications, authorized by the FDA, to treating physicians. The CDC Parasitic Diseases Drug Service provides treatment drugs for patients with parasitic diseases, including travelers, immigrants and refugees from endemic countries. Methods CDC’s records for patients for whom drug was released over a 10-year period were reviewed. Results From 2010–2019, the annual number of drug releases for patient treatment ranged from 21–113 (median 99). Benznidazole, a treatment for Chagas disease, was the most common drug released for patients between 2012–2018, ranging from 42–63% of total drug releases annually. Sodium stibogluconate (Pentostam® 1), for treatment of certain presentations of cutaneous, visceral, and mucocutaneous leishmaniasis, accounted for 6–22% of annual releases over the last 10 years. While requests for treatment for human African trypanosomiasis are rare, in 2019 CDC released eflornithine and nifurtimox for one patient who met criteria for treatment according to the 2019 WHO recommendations.2 Conclusion Recent changes to release frequency of triclabendazole, benznidazole, nifurtimox, and sodium stibogluconate are likely due to FDA-approval and commercial availability of previously investigational drugs. Triclabendazole is now FDA approved for treatment of Fasciola infection in persons ≥6 years old and benznidazole is now FDA approved for treatment of Chagas disease in children 2–12 years old. Miltefosine has also been approved by FDA for treatment of certain leishmaniasis infections. CDC has successfully pursued expiry extensions of drugs with manufacturers, FDA, and other partners to ensure continued domestic availability of treatment options when there has been no or limited production of newer lots. CDC’s Parasitic Diseases Branch can be reached by telephone: 404-718-4745 or email: [email protected]. 1 Pentostam® is made by GlaxoSmithKline 2 WHO interim guidelines for treatment of gambiense HAT. Geneva: 2019. Disclosures All Authors: No reported disclosures


2019 ◽  
Author(s):  
Labanté Outcha Daré ◽  
Pierre-Emile Bruand ◽  
Daniel Gérard ◽  
Benoît Marin ◽  
Valérie Lameyre ◽  
...  

Abstract Although they are declining worldwide, neurotropic parasitic diseases are still common in developing and emerging countries. The aim of this study was to estimate the pooled prevalence and pooled association measures of comorbidities between mental disorders (anxiety, depression, bipolar disorder, and schizophrenia) and neurotropic parasitic diseases (malaria, cysticercosis, toxoplasmosis, human African trypanosomiasis, Chagas disease, and human toxocariasis) in developing and emerging countries. As the first meta-analysis on this topic, this study was performed in accordance with PRISMA guidelines. The protocol was registered in PROSPERO (N°CRD42017056521). The Medline, Embase, Lilacs, and Institute of Epidemiology and Tropical Neurology databases were used to search for articles without any restriction in language or date. We evaluated the quality of studies independently by two investigators using the Downs and Black assessment grid and pooled estimates using the random-effects method from CMA (Comprehensive Meta Analysis) Version 3.0. In total, 18 studies published between 1997 and 2016 met our inclusion criteria. We found that the prevalence of anxiety and depression in people suffering from Chagas disease and/or neurocysticercosis was 44.9% (95% CI, 34.4 – 55.9). In 16 pooled studies that included 1,782 people with mental disorders and 1,776 controls, toxoplasmosis and/or toxocariasis were associated with increased risk of schizophrenia and/or bipolar disorders (odds ratio = 2.3; 95% CI, 1.7 – 3.2). Finally, toxocariasis and/or toxoplasmosis were associated with an increased risk of the onset of schizophrenia (odds ratio = 2.4; 95% CI, 1.7 – 3.4). Our pooled estimates show that the associations between diseases studied are relatively high in developing and emerging countries. This meta-analysis supports the hypothesis that toxoplasmosis could be the cause of schizophrenia. These findings could prove useful to researchers who want to further explore and understand the associations studied. Keywords: Meta-analysis, association, co-morbidities, mental disorders, neurotropic parasitic diseases.


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